Development of the viscosity biosensor for the detection of DNase I based on the flow distance on the paper with DNA mucus.

Deoxyribonuclease I (DNase I) is a biomarker which has important applications in various biological processes. Thus, it is highly important to develop a user-friendly method for the detection of DNase I. Here, we present a paper-based distance sensor for the rapid detection of DNase I based on changes in the viscosity of DNA mucus. The viscosity of DNA mucus varies with different concentrations of DNase I, showing different water flow lengths on the pH test papers, this makes the quantification of DNase I possible. This method has a wide linear range (0.01-10 U/mL), excellent sensitivity, remarkable specificity and excellent reproducibility. The detection limit reaches 0.003 U/mL. Additionally, it can be well applied to detection of DNase I inhibitors, assay of DNase I in human serum and quality evaluation of nucleic acid scavengers. In general, this study offers a brief, convenient, label-free, and economical method to construct paper-based distance sensors using DNA mucus, which is very promising in the detection of DNase I in various applications.

Harmonic components of photoplethysmography and pathological patterns: A cross-sectional study.

This study aimed to examine whether the 3 harmonic components (HCs) of photoplethysmography (PTG) - total harmonic distortion (THD), harmonic power (HP), and normalized harmonic amplitude (HA) - have aging effects and may serve as an arterial stiffness marker and examine the relationship between HCs and clinical severity of pathological patterns. This study had a retrospective chart review design, and electronic medical records of 173 female patients (age: 38.57 ± 11.64 years) were reviewed. Patients were asked to complete the phlegm, blood stasis (BS), and food retention (FR) pattern questionnaires and underwent PTG and the second derivative of PTG measurements. THD, HP, and HA data were extracted till the 12th HCs from the raw PTG data. THD and HA had an aging effect (ß: -0.179 to -0.278) and were related to b/a (r: -02.76 to -0.455) and d/a (r: 0.265-0.360) of the second derivative of PTG. In the younger group (≤33 years), HP and HA were positively correlated with phlegm, BS, and FR patterns (r: 0.257-0.370), while HP was positively correlated with the FR pattern (r: 0.278-0.315) in the middle age group (34-45 years). In the older group (≥46 years), HP and HA were positively or negatively correlated with the phlegm pattern (r: ±0.263 to ±0.440). HCs may serve as an arterial stiffness marker, and may be partially related to phlegm, BS, and FR patterns. Aging effect needs to be considered when utilizing HCs as an indicator of phlegm, BS, and FR patterns.

Community Structure and Predicted Functions of Actively Growing Bacteria Responsive to Released Coral Mucus in Surrounding Seawater.

A direct relationship exists between diverse corals and fish farming in Keten Bay, Amami-Oshima, Japan. The release of coral mucus has a significant impact on the microbial activity of surrounding seawater. To obtain a more detailed understanding of biogeochemical cycles in this environment, the effects of coral mucus on the community structure and function of bacteria in surrounding seawater need to be elucidated. We herein used a bromodeoxyuridine approach to investigate the structures and functions of bacterial communities growing close to mucus derived from two different Acropora corals, AC1 and AC2. The alpha diversities of actively growing bacteria (AGB) were lower in mucus-containing seawater than in control seawater and their community structures significantly differed, suggesting that the growth of specific bacteria was modulated by coral mucus. Rhodobacteraceae and Cryomorphaceae species were the most dominant AGB in response to the mucus of Acropora AC1 and AC2, respectively. In contrast, the growth of Actinomarinaceae, Alteromonadaceae, Flavobacteriaceae, and SAR86 clade bacteria was inhibited by coral mucus. The results of a Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) ana-lysis suggested that the predicted functions of AGB in mucus-containing seawater differed from those in seawater. These functions were related to the biosynthesis and degradation of the constituents of coral mucus, such as polysaccharides, sugar acids, and aromatic compounds. The present study demonstrated that complex bacterial community structures and functions may be shaped by coral mucus, suggesting that corals foster diverse bacterial communities that enhance the ecological resilience of this fish farming area.

[A CASE OF SUSPECTED ALLERGIC BRONCHOPULMONARY MYCOSIS CAUSED BY SCEDOSPORIUM APIOSPERMUM THAT SHOWED CLINICAL IMPROVEMENT AFTER BRONCHOSCOPIC REMOVAL OF A MUCUS PLUG].

A 69-year-old woman presented with a persistent cough and high fever. Thoracic computed tomography revealed atelectasis and high-attenuation mucus. The blood test results showed eosinophils at 18.2%, an absolute eosinophil count of 980 cells/µL, and a total serum immunoglobulin E of 1980IU/mL. Bronchoscopy revealed a mucous plug, which upon photomicrograph examination, showed eosinophils. A culture study of the mucus yielded Scedosporium apiospermum, leading to the suspicion of allergic bronchopulmonary mycosis (ABPM) caused by the fungus. After the bronchoscopic removal of the mucous plug, her symptoms quickly diminished. She was successfully treated without medication, and ABPM has not recurred for 2 years. To our knowledge, ABPM caused by Scedosporium apiospermum is rare, and close follow-up was effective without the administration of systemic steroids or antifungal drugs.

Perception and clinical practice regarding mucus clearance devices with chronic obstructive pulmonary disease: a cross-sectional study of healthcare providers in Saudi Arabia.

OBJECTIVES: Clearing secretions from the airway can be difficult for people with chronic obstructive pulmonary disease (COPD). Mucus clearance devices (MCDs) are an option in disease management to help with this, but healthcare provider awareness and knowledge about them as well as current clinical practice in Saudi Arabia are not known. DESIGN: A cross-sectional online survey consisting of four themes; demographics, awareness, recommendations and clinical practice, for MCDs with COPD patients. SETTING: Saudi Arabia. PARTICIPANTS: 1188 healthcare providers including general practitioners, family physicians, pulmonologists, nursing staff, respiratory therapists and physiotherapists. PRIMARY OUTCOME MEASURES: Healthcare providers' level of awareness about MCDs, and the identification of current clinical practices of COPD care in Saudi Arabia. RESULTS: 1188 healthcare providers (44.4% female) completed the survey. Regarding devices, 54.2% were aware of the Flutter, 23.8% the Acapella and 5.4% the positive expiratory pressure mask. 40.7% of the respondents identified the Acapella, and 22.3% the Flutter as first choice for COPD management. 75% would usually or always consider their use in COPD patients reporting daily difficulty clearing mucus, whereas 55.9% would sometimes or usually consider the use of MCDs with COPD patients who produced and were able to clear mucus with cough. In clinical practice, 380 (32%) of the respondents would prescribe MCDs, 378 (31.8%) would give MCDs without prescriptions, 314 (26.4%) would not provide them at all and 116 (9.8%) would only advise patients about them. CONCLUSION: Healthcare providers are aware of the existence of MCDs and their benefits for sputum clearance and believe that MCDs are beneficial for sputum clearance in some COPD patients. TRIAL REGISTRATION NUMBER: ISRCTN44651852.

Comparative mucomic analysis of three functionally distinct Cornu aspersum Secretions.

Every animal secretes mucus, placing them among the most diverse biological materials. Mucus hydrogels are complex mixtures of water, ions, carbohydrates, and proteins. Uncertainty surrounding their composition and how interactions between components contribute to mucus function complicates efforts to exploit their properties. There is substantial interest in commercializing mucus from the garden snail, Cornu aspersum, for skincare, drug delivery, tissue engineering, and composite materials. C. aspersum secretes three mucus-one shielding the animal from environmental threats, one adhesive mucus from the pedal surface of the foot, and another pedal mucus that is lubricating. It remains a mystery how compositional differences account for their substantially different properties. Here, we characterize mucus proteins, glycosylation, ion content, and mechanical properties that could be used to provide insight into structure-function relationships through an integrative "mucomics" approach. We identify macromolecular components of these hydrogels, including a previously unreported protein class termed Conserved Anterior Mollusk Proteins (CAMPs). Revealing differences between C. aspersum mucus shows how considering structure at all levels can inform the design of mucus-inspired materials.

Pseudomonas aeruginosa type IV pili actively induce mucus contraction to form biofilms in tissue-engineered human airways.

The opportunistic pathogen Pseudomonas aeruginosa causes antibiotic-recalcitrant pneumonia by forming biofilms in the respiratory tract. Despite extensive in vitro experimentation, how P. aeruginosa forms biofilms at the airway mucosa is unresolved. To investigate the process of biofilm formation in realistic conditions, we developed AirGels: 3D, optically accessible tissue-engineered human lung models that emulate the airway mucosal environment. AirGels recapitulate important factors that mediate host-pathogen interactions including mucus secretion, flow and air-liquid interface (ALI), while accommodating high-resolution live microscopy. With AirGels, we investigated the contributions of mucus to P. aeruginosa biofilm biogenesis in in vivo-like conditions. We found that P. aeruginosa forms mucus-associated biofilms within hours by contracting luminal mucus early during colonization. Mucus contractions facilitate aggregation, thereby nucleating biofilms. We show that P. aeruginosa actively contracts mucus using retractile filaments called type IV pili. Our results therefore suggest that, while protecting epithelia, mucus constitutes a breeding ground for biofilms.

[Clinical characteristics and risk factors for bronchoscopic airway mucus hypersecretion in childhood pneumonia infected by different pathogens].

Objective: To investigate the risk factors for airway mucus hypersecretion in childhood pneumonia infected by different pathogens. Method: A retrospective cohort included 968 children who were hospitalized for Mycoplasma pneumoniae pneumonia (MPP), respiratory syncytial virus (RSV) pneumonia, adenovirus pneumonia and underwent bronchoscopy in Respiratory Department of Children's Hospital of Chongqing Medical University from January 2019 to December 2021 was conducted. The children were divided into two groups distinguished by airway mucus secretion according to the airway mucus hypersecretion score which were scored according to the mucus secretion under the bronchoscope. The demographic characteristics, clinical characteristics, laboratory tests and disease severity of the two groups were compared. And the risk factors for the development of airway mucus hypersecretion in two groups were analyzed. Chi square test, Mann-Whithey U test and Fisher exact test were used to analyze the differences between the two groups, and multivariate Logistic regression was used to analyze the influencing factors. Result: There were 559 males and 409 females in the 968 children, with an age of 4.0 (1.4, 6.0) years. Among the 642 children with MPP, 185 cases were in the hypersecretion group and 457 cases were in the non-hypersecretion group. There were 41 cases in the hypersecretion group and 160 cases in the non-hypersecretion group of 201 children with RSV pneumonia. In the 125 children with adenovirus pneumonia, there were 39 cases in the hypersecretion group and 86 cases in the non-hypersecretion group. In these children, the age of children in the hypersecretion group was older than that in the non-hypersecretion group (6.0 (4.0, 7.0) vs. 5.0 (3.0, 7.0) years old, 1.5 (0.5, 3.6) vs. 0.8 (0.4, 1.6) years old, 2.0 (1.2, 4.5) vs. 1.3 (0.8, 2.0) years old, U=35 295.00, 2 492.00, 1 101.00, all P<0.05). Through multivariate Logistic regression analysis it found that increased risk of airway mucus hypersecretion was present in childhood MPP with increase in peripheral blood white blood cell count (OR=3.30, 95%CI 1.51-7.93, P=0.004) or increase in neutrophil ratio (OR=2.24, 95%CI 1.16-4.33, P=0.016) or decrease in lymphocyte count (OR=3.22, 95%CI 1.66-6.31, P<0.001) or decrease in serum albumin (OR=2.00, 95%CI 1.01-3.98, P=0.047). The risk of airway mucus hypersecretion was increased in children with RSV pneumonia combined with elevated peripheral blood eosinophils (OR=3.04, 95%CI 1.02-8.93, P=0.043). Meanwhile, airway mucus hypersecretion was associated with severe pneumonia (OR=2.46, 95%CI 1.03-6.15, P=0.047) in children with RSV pneumonia. Older age was associated with increased risk of airway mucus hypersecretion in children with adenovirus pneumonia (OR=1.02, 95%CI 1.00-1.04, P=0.026). In these children with occurrence of pulmonary rales, wheezes or sputum sounds (OR=3.65, 95%CI 1.22-12.64, P=0.028) had an increased risk of airway mucus hypersecretion. Neutrophils in bronchoalveolar lavage fluid (BALF) demonstrated higher ratio in hypersecretion group from children with MPP (0.65 (0.43, 0.81) vs. 0.59 (0.34, 0.76), U=24 507.00, P<0.01), while the proportion of macrophages in BALF was lower (0.10 (0.05, 0.20) vs. 0.12 (0.06, 0.24), U=33 043.00, P<0.05). Nucleated cell count and neutrophil ratio in BALF were higher in hypersecretion group of children with RSV pneumonia (1 210 (442, 2 100)×106 vs. 490 (210, 1 510)×106/L, 0.43 (0.26, 0.62) vs. 0.30 (0.13, 0.52), U=2 043.00, 2 064.00, all P<0.05). Conclusions: The increase in peripheral blood white blood cell count, neutrophil ratio and decrease in lymphocyte count, serum albumin in children with MPP is related to the development of airway mucus hypersecretion. In children with RSV pneumonia, the abnormal increase of eosinophils in peripheral blood has relationship with hypersecretion. The appearance of lung rale, wheezing, and sputum rale are associated with airway mucus hypersecretion in children with adenovirus pneumonia. In addition, local neutrophil infiltration in the respiratory tract is closely related to the occurrence of airway mucus hypersecretion caused by Mycoplasma pneumoniae and RSV infection.

Mucin-binding adhesins: A key to unlocking the door of mutualism.

From corals to mammals, mucus is a conserved feature that prevents microbes from accessing the surfaces that produce it. However, interactions between mucus and microbes remain poorly understood. In this issue of Cell Host & Microbe, Smith et al. unveil that mucus binding by bacteria is crucial for host-microbe symbiosis.

Biological properties of mucus from land snails (Lissachatina fulica) and freshwater snails (Pomacea canaliculata) and histochemical study of mucous cells in their foot.

Background: Mucus derived from many land snails has been extensively utilised in medicine and cosmetics, but some biological activities of the mucus need to be well documented. Nevertheless, most mucus is obtained from land snails, while mucus from freshwater snails has yet to be attended. Methods: This study aims to determine and compare mucus's antioxidant and anti-inflammatory activities from the land snail Lissachatina fulica and the freshwater snail Pomacea canaliculata. ABTS, DPPH, reducing power and total antioxidant activity assays were used to evaluate the antioxidant capacity. Inhibition of nitric oxide production in lipopolysaccharide-activated RAW 264.7 cells was performed to determine the anti-inflammatory activity. Additionally, the histochemical analysis of mucous cells in each snail foot was conducted to compare the distribution of mucous cells and types of mucins using periodic acid-Schiff and Alcian blue staining. Results: Mucus from L. fulica and P. canaliculata exhibited antioxidant and anti-inflammatory activities in different parameters. L. fulica mucus has higher total antioxidant (44.71 ± 2.11 mg AAE/g) and nitric oxide inhibitory activities (IC50 = 9.67 ± 0.31 µg/ml), whereas P. canaliculata mucus has better-reducing power activity (43.63 ± 2.47 mg AAE/g) and protein denaturation inhibition (IC50 = 0.60 ± 0.03 mg/ml). Histochemically, both species' dorsal and ventral foot regions contained neutral and acid mucins in different quantities. In the dorsal region, the neutral mucins level in L. fulica (16.64 ± 3.46%) was significantly higher than that in P. canaliculata (11.19 ± 1.50%), while the acid mucins level showed no significant difference between species. Levels of both mucins in the ventral foot region of L. fulica (15.08 ± 3.97% and 10.76 ± 3.00%, respectively) were significantly higher than those of P. canaliculata (2.25 ± 0.48% and 2.71 ± 0.56%, respectively). This study revealed scientific evidence of the biological capacity of mucus from L. fulica and P. canaliculata as well as provided helpful information on the region of the foot which produces effective mucus.

Broadly neutralizing antibodies consistently trap HIV-1 in fresh cervicovaginal mucus from select individuals.

In addition to direct neutralization and other classical effector functions, IgG possesses a little recognized and thus under-utilized effector function at mucosal surfaces: Fc-mucin bonds enable IgG to trap viruses in mucus. Due to the paucity of envelope glycoproteins that limits the number of IgG that can bind HIV, it remains poorly understood whether IgG-mucin interactions can effectively immobilize HIV in human cervicovaginal mucus (CVM). Here, we obtained 54 fresh, undiluted CVM specimens from 17 different women, and employed high-resolution multiple particle tracking to quantify the mobility of fluorescent HIV virus-like-particles in CVM treated with various HIV-specific IgG. We observed consistent and effective trapping of HIV by broadly neutralizing antibodies (VRC01, PGT121, and 2F5) in a subset of women. While trapping efficacy was not affected by the menstrual cycle, it was positively correlated with appreciable L. Crispatus populations in the microbiome, and negatively correlated with appreciable L. Iners or G. Vaginalis populations. Our work demonstrates for the first time that IgG-mucin crosslinking is capable of reinforcing the mucosal barrier against HIV, and motivates further investigation of passive immunization against vaginal transmission of STIs. STATEMENT OF SIGNIFICANCE: HIV transmission in women primarily occurs vaginally, yet the 3-way interactions between mucins and HIV virions mediated by HIV-binding antibodies in cervicovaginal mucus (CVM) is not well understood. While IgG-Fc possess weak affinity to mucins that trap virus/IgG complexes in mucus, the effectiveness against HIV remains unclear, due to the low number of virion-bound IgG. Here, we discovered that IgG can trap HIV consistently in CVM from select individuals regardless of their birth control status or menstrual cycle phase. IgG-mediated trapping of HIV was moderately associated with microbiome composition. These results suggest that IgG-mucin interactions could potentially reduce HIV transmission and highlight the importance of mucosal secretions in antibody-mediated prevention of HIV and other sexually transmitted infections.

Mucus Hypersecretion in Chronic Obstructive Pulmonary Disease and Its Treatment.

Most patients diagnosed with chronic obstructive pulmonary disease (COPD) present with hallmark features of airway mucus hypersecretion, including cough and expectoration. Airway mucus function as a native immune system of the lung that severs to trap particulate matter and pathogens and allows them to clear from the lung via cough and ciliary transport. Chronic mucus hypersecretion (CMH) is the main factor contributing to the increased risk of morbidity and mortality in specific subsets of COPD patients. It is, therefore, primarily important to develop medications that suppress mucus hypersecretions in these patients. Although there have been some advances in COPD treatment, more work remains to be done to better understand the mechanism underlying airway mucus hypersecretion and seek more effective treatments. This review article discusses the structure and significance of mucus in the lungs focusing on gel-forming mucins and the impacts of CMH in the lungs. Furthermore, we summarize the article with pharmacological and nonpharmacological treatments as well as novel and interventional procedures to control CMH in COPD patients.

Mirror Image Mucins and Thio Mucins with Tunable Biodegradation.

Mucin glycoproteins are the major component of mucus and are integral to the cellular glycocalyx. Mucins play diverse roles in health and disease, are an important element in epithelial tissue models, and have broad therapeutic potential. All mucin applications are currently challenged by their inherent structural heterogeneity and degradation by proteases. In this study, we describe the synthesis and study of chemically defined mucin analogues bearing native glycans. We utilized combinations of enantiomer amino acids and glycan thioether linkages to achieve tunable proteolysis while maintaining cytocompatibility and binding activity. Structural characterization revealed a previously unknown mirror-image helix and sheds light on the molecular drivers of glycoprotein conformation. This work represents an important step toward the development of artificial mucins for biomedical applications.

Intestinal mucus and their glycans: A habitat for thriving microbiota.

The colon mucus layer is organized with an inner colon mucus layer that is impenetrable to bacteria and an outer mucus layer that is expanded to allow microbiota colonization. A major component of mucus is MUC2, a glycoprotein that is extensively decorated, especially with O-glycans. In the intestine, goblet cells are specialized in controlling glycosylation and making mucus. Some microbiota members are known to encode multiple proteins that are predicted to bind and/or cleave mucin glycans. The interactions between commensal microbiota and host mucins drive intestinal colonization, while at the same time, the microbiota can utilize the glycans on mucins and affect the colonic mucus properties. This review will examine this interaction between commensal microbes and intestinal mucins and discuss how this interplay affects health and disease.

Altered Secretion, Constitution, and Functional Properties of the Gastrointestinal Mucus in a Rat Model of Sporadic Alzheimer's Disease.

The gastrointestinal (GI) system is affected in Alzheimer's disease (AD); however, it is currently unknown whether GI alterations arise as a consequence of central nervous system (CNS) pathology or play a causal role in the pathogenesis. GI mucus is a possible mediator of GI dyshomeostasis in neurological disorders as the CNS controls mucus production and secretion via the efferent arm of the brain-gut axis. The aim was to use a brain-first model of sporadic AD induced by intracerebroventricular streptozotocin (STZ-icv; 3 mg/kg) to dissect the efferent (i.e., brain-to-gut) effects of isolated central neuropathology on the GI mucus. Morphometric analysis of goblet cell mucigen granules revealed altered GI mucus secretion in the AD model, possibly mediated by the insensitivity of AD goblet cells to neurally evoked mucosal secretion confirmed by ex vivo cholinergic stimulation of isolated duodenal rings. The dysfunctional efferent control of the GI mucus secretion results in altered biochemical composition of the mucus associated with reduced mucin glycoprotein content, aggregation, and binding capacity in vitro. Finally, functional consequences of the reduced barrier-forming capacity of the mucin-deficient AD mucus are demonstrated using the in vitro two-compartment caffeine diffusion interference model. Isolated central AD-like neuropathology results in the loss of efferent control of GI homeostasis via the brain-gut axis and is characterized by the insensitivity to neurally evoked mucosal secretion, altered mucus constitution with reduced mucin content, and reduced barrier-forming capacity, potentially increasing the susceptibility of the STZ-icv rat model of AD to GI and systemic inflammation induced by intraluminal toxins, microorganisms, and drugs.

Bronchoscopy for refractory/unexplained cough with mucus.

INTRODUCTION: Refractory/unexplained cough (RUCC) is typically associated with throat symptoms and a dry cough. Some patients attending specialist cough clinics however, report sputum production (>1 tablespoon daily) and atypical sensations (urge-to-cough in chest). Bronchoscopy findings in this specific cohort have rarely been described. AIMS: We aimed to evaluate bronchoscopy, bronchoalveolar lavage (BAL) cell differential and microbiology findings in RUCC with mucus production. METHODS: We retrospectively reviewed case notes, procedure results and treatment of patients undergoing bronchoscopy for RUCC with more than a tablespoon of sputum daily. RESULTS: Data were included from 54 patients with RUCC, normal or trivial findings on CT (Computerised Tomography) imaging and no response to guideline-directed treatment of their cough. Most (84%) patients had BAL neutrophilia and excessive dynamic airway collapse (EDAC) was seen in 31%. Treatment strategies in these patients differed to those adopted in typical RUCC associated with a dry cough. Management was influenced or changed in 48/54 (89%) of the patients undergoing bronchoscopy. CONCLUSIONS: Bronchoscopy provides high diagnostic value in RUCC with mucus production (>1 tbsp daily), identifying specific treatable traits including neutrophilic airway inflammation and EDAC.

Imaging Regional Airway Involvement of Asthma: Heterogeneity in Ventilation, Mucus Plugs and Remodeling.

The imaging of asthma using chest computed tomography (CT) is well-established (Jarjour et al., Am J Respir Crit Care Med 185(4):356-62, 2012; Castro et al., J Allergy Clin Immunol 128:467-78, 2011). Moreover, recent advances in functional imaging of the lungs with advanced computer analysis of both CT and magnetic resonance images (MRI) of the lungs have begun to play a role in quantifying regional obstruction. Specifically, quantitative measurements of the airways for bronchial wall thickening, luminal narrowing and distortion, the amount of mucus plugging, parenchymal density, and ventilation defects that could contribute to the patient's disease course are instructive for the entire care team. In this chapter, we will review common imaging methods and findings that relate to the heterogeneity of asthma. This information can help to guide treatment decisions. We will discuss mucous plugging, quantitative assessment of bronchial wall thickening, delta lumen phenomenon, parenchymal low-density lung on CT, and ventilation defect percentage on MRI as metrics for assessing regional ventilatory dysfunction.

Lactobacillus rhamnosus 76 alleviates airway inflammation in ovalbumin-allergic mice and improves mucus secretion by down-regulating STAT6/SPDEF pathway.

Previous studies have reported a correlation between the dysregulation of intestinal microbiota and the occurrence of asthma. This study aimed to investigate the effect of probiotic Lactobacillus rhamnosus 76 (LR76) on ovalbumin (OVA)-allergic mice and the mechanism of LR76 affecting mucus secretion in asthma. OVA-allergic mice were supplemented with LR76, and 16HBE cells induced by interleukin-13 (IL-13) were treated with LR76 supernatant (LR76-s) to observe the effect of LR76. In OVA-sensitized mice, LR76 alleviated the inflammatory cell infiltration in lung tissue and reduced the inflammatory cell counts of BALF. The expression level of mRNA, including Il4, Il5, Il13, Il25, Tgfb1, Il10, and Ifng, was decreased in the lung tissue of mice in the LR76 group compared with the OVA group. MUC5AC expression was down-regulated, while SCGB1A1 was up-regulated in the lung tissue of OVA-allergic mice after being supplemented with LR76 and in 16HBE cells induced by IL-13 after incubating with LR76-s. LR76 and LR76-s down-regulated the expression of proteins, including STAT6, p-STAT6, and SPDEF, and mRNA of STAT6 and SPDEF. In conclusion, LR76 alleviated airway inflammation and Th2 response in OVA-allergic mice and improved the mucus secretion of mouse lung tissue and 16HBE cells in the asthma model by down-regulating STAT6/SPDEF pathway.

TNF-α and MMPs mediated mucus hypersecretion induced by cigarette smoke: An in vitro study.

Cigarette smoke is one of the leading causes of oxidative stress due to high levels of free radicals, which in turn leads to the degradation of alveolar cell walls and development of emphysema. Cigarette smoking has been linked to chronic bronchitis, Chronic Obstructive Pulmonary Disease (COPD) and lung cancer as well. The aim of the present study was to observe the effect of cigarette smoke extract (CSE) on TNF-α and MMPs mediated mucus hypersecretion in A549 cell line. The MTT experiments showed that CSE caused a dose-dependent decline in the level of viability of A549 cells. In addition, AO/PI and Mitotracker Red staining assays demonstrated that CSE caused the A549 cells to undergo apoptosis. This was determined by observing the reduction in mitochondrial membrane potential. CSE was found to be responsible for the formation of intracellular ROS, which was observed by DCFDA staining through fluorescence microscopy. Approximately 65% migration rate was decreased in 20% CSE exposed cells. CSE exposure led to the significantly increased mRNA levels of TNF-α, MMP-7, and MMP-12, in comparison to the control cells. Additionally, the expression of MUC5AC and MUC5B was provoked by CSE as well. Human epithelial cells are stimulated by TNF-α and MMPs secreted mucus, as shown by expression of MUC5AC and MUC5B. CSE could induce mucus in lungs through TNF-α and MMPs mediated pathways.

Chitooligosaccharide reconstitutes intestinal mucus layer to improve oral absorption of water-soluble drugs.

Intestinal mucus is a complex natural hydrogel barrier with unique physical properties that impede the absorption of various oral drugs. Both washout from the upper water layer and the physical resistance of the mucus layer particularly affect bioavailability of, especially, highly water-soluble molecules. One potential strategy for designing pharmaceutical formulations is to add absorption enhancers (AEs). However, there are few reports of AEs that work on mucus and their underlying mechanisms, leading to imprecise application. In this study, we investigated chitooligosaccharide (COS) as a safe, low-cost, and effective oral drug AE. We revealed the hydrodynamic law of interaction between COS and the intestinal mucus layer, which was associated with absorption benefiting mucus structural reconstruction. Based on this, we designed a translational strategy to improve the bioavailability of a group of soluble oral drugs by drinking COS solution before administration. Moreover, this research is expected to expand its application scenario by reducing drug dosage such as avoiding gastro-intestinal irritation and slowing veterinary antibiotic resistance.